DESCRIPTION: (Applicant's Abstract) Drug craving or intense wanting associated with cocaine (crack) dependence represents a generally recognized cause of the chronically relapsing nature of cocaine abuse. A major premise of this R21 proposal is that knowing where in the human brain the correlates of cocaine craving are localized would provide essential direction to the heretofore unsuccessful development of treatments aimed at curbing drug craving. This research plan would use guided imagery as individualized internal cues for the provocation of drug craving and control conditions and Positron Emission Tomography (PET) to map their neural correlates. The proposed experiments would test the following hypotheses: that drug craving associated with cocaine versus nicotine dependence involves the activation of similar neural pathways; that important sex differences exist in the neural correlates of cocaine craving in dependent individuals; and that the subjective states of drug craving and drug "liking" are associated with distinct brain activation maps. Hypothesis testing will involve the following specific aims: Specific aim #1 would compare the neural correlates of human drug craving associated with crack cocaine versus nicotine dependence. Task-related changes in regional Cerebral Blood Flow (rCBF) would be compared in cocaine-dependent who are not nicotine users and nicotine-dependent men who are not cocaine users. Drug craving, and the control conditions (anger, neutral episodic memory recall), would be induced by guided imagery of personalized scripts. Specific aim #2 would examine sex differences in the neural correlates of cocaine craving associated with crack cocaine dependence. A group of cocaine-dependent women, well matched to the men studied in aim #1, would be submitted to the identical PET neuroactivation analysis of internally generated cocaine craving. Specific aim #3 would compare the neural correlates of the urge for cocaine use in cocaine-dependent and occasional, non-dependent crack users. A group of occasional crack users, well matched to the cocaine-dependent men studied in aim #1, would be submitted to an identical PET neuroactivation analysis of the subjective states of drug craving and drug liking in dependent and non-dependent cocaine users, respectively. The design of the proposed studies involve the use of multiple control conditions to isolate the neural correlates of cue-induced cocaine craving and the use of both subjective and objective measures of cue response.